Sodium Carbonate → 7-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine

HRID 1262421Notes

Reaction equation

HRID 1262421 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[F:13][C:14]1([F:26])[O:18][C:17]2[CH:19]=[CH:20][CH:21]=[C:22](B(O)O)[C:16]=2[O:15]1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:14]1([F:13])[O:15][C:16]2[CH:22]=[CH:21][CH:20]=[C:19]([C:2]3[N:10]4[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]4)=[CH:4][CH:3]=3)[C:17]=2[O:18]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 16427145(2,2-Difluoro-1,3-dioxaindan-4-yl)boronic acidHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 667125177-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazineYield 63%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.531 g, 2.18 mmol), 2,2-Difluorobenzo[1,3]dioxole-4-boronic acid (0.624 g, 3.09 mmol), Tetrakis(triphenylphosphine)palladium(0) (125 mg, 0.108 mmol), 2.00 M of Sodium carbonate in Water (2.70 mL), and 1,4-Dioxane (6.6 mL) were combined in a vial, degassed (freeze-pump-thaw) and was heated under an atmosphere of Nitrogen at 80° C. overnight. Conversion was ˜75%. Further heating for a second night lead to little additional product relative to bromide. The mixture was diluted with water (20 mL) then extracted with EtOAc (3×30 mL). The org. was washed with brine, dried, filtered through 7 mL silica gel, washing with EtOAc, then conc. in vacuo onto 7 g silica gel. Purification on an ISCO (80 g, 0-10% EtOAc:Hex) afforded first an impurity, then the product 7-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.440 g; Yield=63.0%). LCMS (HPLC): 1.46 min, 322 (M+H); 1H-NMR (DMSO-d6): 9.12 (s, 1H), 8.16 (d, 1H, J=8.1 Hz), 7.48 (d, 1H, J=7.9 Hz), 7.40 (m, 1H), 7.33 (d, 1H, J=4.8 Hz), 7.16 (d, 1H, J=4.8 Hz), 2.55 (s, 3H).

Workup

  1. customdegassed (freeze-pump-thaw)
  2. temperatureFurther heating for a second night lead to little additional product relative to bromide
  3. additionThe mixture was diluted with water (20 mL)
  4. extractionthen extracted with EtOAc (3×30 mL)
  5. washwas washed with brine
  6. customdried
  7. filtrationfiltered through 7 mL silica gel
  8. washwashing with EtOAc
  9. customPurification on an ISCO (80 g, 0-10% EtOAc:Hex)
  10. customafforded first an impurity

Sources & evidence

ORD record
ord-dbba9a22ad854f7f8a451e58dca81308
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…